A Phase 2 interventional study of Alpha-1-Antitrypsin (AAT) in Graft vs Host Disease, sponsored by University of Michigan Rogel Cancer Center. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-11-27.
Sponsored by University of Michigan Rogel Cancer Center · Phase 2, Interventional, and Treatment
This clinical trial will study the safety and efficacy of using the drug Zemaira, an Alpha 1-Antitrypsin (AAT) medication (also known as an Alpha1-Proteinase Inhibitor [Human]) for the treatment of steroid refractory GVHD.
For bone marrow transplant patients, the most common, serious complication is Graft vs Host Disease (GVHD), which at its most severe is a life-threatening, complication and a significant cause of treatment related death, following stem cell transplantation. GVHD is a major obstacle to the overall success of transplant treatment, a strategy that would otherwise provide the possibility of a cure for patients with blood cancers or severe blood disorders. GVHD primarily affects the skin, gut, and liver of the recipient, and involves the interaction of the recipient's (the host's) cells and tissues with the donor's immune system cells that see the host tissues as foreign, and attack the host's cells resulting in tissue and organ damage.
The severity of acute GvHD ranges from mild to severe, and for patients who don't respond to steroid therapy, the complication is nearly always fatal, either from organ damage or opportunistic infection as a consequence of high dose, steroid treatments.
There is currently no known effective therapy for patients with acute graft vs host disease that's refractory (nonresponsive) to steroid therapy. As stated earlier,the overwhelming majority of these patients may ultimately die from infection. The incidence of acute GvHD that requires intervention, is higher for unrelated donor transplants, the most common treatment option available, and therefore, these patients are at higher risk for treatment related complications from GVHD. Approximately 20,000 unrelated donor transplants are performed each year. The magnitude of this problem then is significant for patients who otherwise might be cured of their blood cancer or disease.
94 studies on the registry are indexed under Alpha 1-Antitrypsin Deficiency; 5 are open to participants now.
This study's enrollment of 40 is above the median of 27 across 58 interventional studies indexed under Alpha 1-Antitrypsin Deficiency.
Browse Alpha 1-Antitrypsin Deficiency studies →University of Michigan Rogel Cancer Center is the lead sponsor of 316 studies on the registry; 46 are open to participants now.
Of its 46 completed or terminated interventional studies of FDA-regulated products, 30 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients must have clinical evidence* of steroid-refractory acute Graft vs Host Disease (any organ) defined as one of the following:
Exclusion Criteria:
Alpha-1-Antitrypsin (AAT) for the treatment of Steroid Refractory Acute Graft vs Host Disease.
Drug: Alpha-1-Antitrypsin (AAT)
AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28. A second course of treatment will not be given.
Also known as: Zemaira
Percentage of Patients That Respond to Treatment
To estimate the proportion of patients with steroid refractory acute Graft vs Host Disease) GvHD who respond (achieve either PR or CR) to Alpha-1 Antitrypsin (AAT) at a dose of 60mg/kg twice weekly for 8 doses Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy. Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
Time frame: 4 weeks
Percentage of Patients Who Achieve a Complete Response to Treatment
To estimate the proportion of patients in complete remission without additional therapy at four weeks after the last dose of AAT Complete remission is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
Time frame: 4 weeks
Percentage of Patients With Documented Infection
To estimate the incidence of infection during and following treatment of steroid refractory acute GVHD with AAT
Time frame: 30 days
The Percentage of Patients Alive at 6 Months for Patients in CR or PR
Survival at 6 months in patients receiving AAT treatment for steroid refractory acute GVHD for patients that achieved a CR or PR. Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy. Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
Time frame: 6 months
Mean Fold Change in Plasma Biomarkers
The fold change in levels of plasma biomarkers IL-6, TNF-alpha and ST2 will be measured pre-treatment and after the administration of AAT treatment for steroid refractory GvHD.
Time frame: Baseline, 2 weeks, and 4 weeks
Mean Plasma Levels for Alpha-1-Antitrypsin (AAT)
Plasma levels of Alpha-1-Antitrypsin(AAT)will be measured.
Time frame: 4 weeks
| Milestone | Treatment Arm |
|---|---|
| Started | 40 |
| Completed | 40 |
| Not completed | 0 |
To estimate the proportion of patients with steroid refractory acute Graft vs Host Disease) GvHD who respond (achieve either PR or CR) to Alpha-1 Antitrypsin (AAT) at a dose of 60mg/kg twice weekly for 8 doses Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy. Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
| percentage of patients | Treatment Arm |
|---|---|
| Percentage of Patients That Respond to Treatment | 65 (48 to 79) |
To estimate the proportion of patients in complete remission without additional therapy at four weeks after the last dose of AAT Complete remission is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
| percentage of patients | Treatment Arm |
|---|---|
| Percentage of Patients Who Achieve a Complete Response to Treatment | 35 (21 to 52) |
To estimate the incidence of infection during and following treatment of steroid refractory acute GVHD with AAT
| percentage of patients | Treatment Arm |
|---|---|
| Percentage of Patients With Documented Infection | 32.5 |
Survival at 6 months in patients receiving AAT treatment for steroid refractory acute GVHD for patients that achieved a CR or PR. Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy. Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
| percentage of patients | Treatment Arm |
|---|---|
| The Percentage of Patients Alive at 6 Months for Patients in CR or PR | 50 (34 to 73) |
The fold change in levels of plasma biomarkers IL-6, TNF-alpha and ST2 will be measured pre-treatment and after the administration of AAT treatment for steroid refractory GvHD.
| fold change from baseline | Treatment Arm |
|---|---|
| IL-6 Fold Change at 2 weeks | 6.3 ± 3.6 |
| IL-6 Fold Change at 4 weeks | 4 ± 1.9 |
| TNF-alpha Fold Change at 2 weeks | 1.7 ± 0.8 |
| TNF-alpha Fold Change at 4 weeks | 1.1 ± 0.2 |
| ST2 Fold Change at 2 weeks | 1.2 ± 0.4 |
| ST2 Fold Change at 4 weeks | 1.5 ± 0.7 |
Plasma levels of Alpha-1-Antitrypsin(AAT)will be measured.
| mg/dl | Treatment Arm |
|---|---|
| AAT levels at two weeks | 196.8 ± 11.91 |
| AAT levels at 4 weeks | 214.8 ± 18.62 |
Collected over Patients will be followed for adverse events for 30 days after the last dose of the study drug.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment Arm | 8/40 (20%) | 11/40 (27.5%) | 31/40 (77.5%) |
| Event | Treatment Arm |
|---|---|
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 3/40 |
| Immune system disorderImmune system disorders | 2/40 |
| SepsisInfections and infestations | 2/40 |
| Disseminated intravascular coagulationBlood and lymphatic system disorders | 1/40 |
| Thrombotic thrombocytopenic purpuraBlood and lymphatic system disorders | 1/40 |
| ColitisGastrointestinal disorders | 1/40 |
| Lower gastrointestinal hemorrhageGastrointestinal disorders | 1/40 |
| Multi-organ failureGeneral disorders | 1/40 |
| Bladder infectionInfections and infestations | 1/40 |
| Hepatic infectionInfections and infestations | 1/40 |
| Event | Treatment Arm |
|---|---|
| InfectionInfections and infestations | 11/40 |
| HyperglycemiaMetabolism and nutrition disorders | 7/40 |
| Blood bilirubin increasedInvestigations | 6/40 |
| Lymphocyte count decreasedInvestigations | 5/40 |
| Platelet count decreasedInvestigations | 5/40 |
| AnemiaBlood and lymphatic system disorders | 4/40 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 4/40 |
| Thrombotic thrombocytopenic purpuraBlood and lymphatic system disorders | 3/40 |
| Lower gastrointestinal hemorrhageGastrointestinal disorders | 3/40 |
| SepsisInfections and infestations | 3/40 |
| Age, Continuous(years) | Treatment Arm |
|---|---|
| Median | 59 (18 to 70) |
| Sex: Female, Male(Participants) | Treatment Arm |
|---|---|
| Female | 13 |
| Male | 27 |
This study is completed, as verified in Oct 2018. You cannot join it, but the record below documents what was studied.
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Alpha 1-Antitrypsin Deficiency→
University of Michigan Rogel Cancer Center